N6-methyladenosine(m6A)is the most abundant modification of RNA methylation,dynamically regulated by"writer"and"eraser",regulating the expression of target genes by modulating key biological processes such as mRNA splicing,stability,and translation,after being recognized and combined by"reader".Recent studies have revealed that m6A modifica-tion can regulate the expression of drug-metabolizing enzymes and transporters,consequently affecting the body's drug meta-bolic rate or intracellular drug concentrations,and ultimately in-fluencing therapeutic outcomes.This article reviews the research progress of the molecular mechanism of m6A modification regula-ting drug-metabolizing enzymes and transporters,so as to pro-vide a new idea for rational and personalized clinicaldrug use.

Objective To explore the application value of Fast Dixon technique in MR hip joint scanning.Methods Fifty young volunteers were recruited to perform axial and coronal MR scans of the hip joint.The scanning sequence was Fast Dixon T2WI sequence and conventional Dixon T2WI sequence.A double-blind five-point scale was used to subjectively evaluate the image quality of the two types sequences.The signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of the axial image were measured at the maximum level of the bladder display.Results In the scores of"good contrast between surrounding tissue and femoral head signal"and"overall image quality",the Fast Dixon T2WI sequence was better than the conventional Dixon T2WI sequence,and the difference was statistically significant(P<0.05).There was no significant difference in the average scores of"whether bladder artifacts affected the diagnosis"and"whether the fat suppression effect was good"between Fast Dixon T2WI sequence and conventional Dixon T2WI sequence(P>0.05).In the objective image quality evaluation,the SNR and CNR of Fast Dixon T2WI sequence were better than those of conventional Dixon T2WI sequence,and the difference was statistically significant(P<0.05).Conclusion The image quality score of the hip joint of young volunteers with Fast Dixon T2WI sequence combined with multiple averaging excitation technique is significantly higher than that of conventional Dixon T2WI sequence.The Fast Dixon T2WI sequence can increase the effect of inhibiting fat and motion artifacts without increasing the scanning time,and the joint face ratio is good.Fast Dixon technique can replace the traditional Dixon technique,thus becoming an optimal choice for hip joint MR scanning.

Objective To evaluate MRI and clinicopathological prognostic factors in predicting disease-free survival(DFS)of stage ⅢC1p cervical cancer patients.Methods A total of 102 stage ⅢC1p cervical cancer patients who underwent surgical treatment were selected.Based on survival status,stage ⅢC1p cases were divided into two subgroups:progression group and no progression group.The influencing factors of clinicopathological indexes and MRI features on prognosis in the two groups were analyzed.Results The results of the univariate analysis showed that squamous cell carcinoma antigen(SCC-Ag)level,T stage and location of lymph node metastasis(LNM)were correlated with the prognosis of stage ⅢC1p cervical cancer patients(P<0.05).Multivariate analysis results showed that late T stage,SCC-Ag>13 ng/mL,and LNM location≥3 were the high risk factors affecting the 3-year DFS decline in stage ⅢC1p cervical cancer patients.Conclusion SCC-Ag,T stage,and LNM location are independent risk factors for 3-year DFS in stage ⅢC1p cervical cancer patients.

Objective To find potential biomarkers and analyzing metabolic pathways of the treatment by honey-processed Hedysari Radix,the cecal contents of rats with spleen-Qi deficiency were used as samples for analysis.Methods Sixty male SD rats were randomly divided into blank,model,experimental and control groups.The rats in other groups except the control group were carried out by using the three-factor compound modeling method of bitter-cold diarrhea,excessive exertion and hunger and satiety disorders.Experimental group was given 12.60 g·kg-1 honey-processed Hedysari Radix;control group was given 0.63 g·kg-1 lactobacillus bifidum triplex tabletsa;control and model groups received with equal volume of distilled water for a total of 15 days.Measure body weight,anal temperature,immune organ index of rats.Ultra-pressure liquid chromatography-quadrupole-exactive-mass spectrometry technology was used to measure the levels of endogenous metabolites in cecum contents.Orthogonal partial least squares discriminant analysis and database"Kyoto Encyclopedia of Genes and Genomes"were used to identify potential differential metabolites and possible metabolic pathways.Results After the intervention,the average body weight of the experimental,control,model and blank groups was(216.87±7.85),(210.96±9.03),(159.47±5.18)and(293.51±22.98)g;anal temperature was(36.14±0.48),(35.40±0.64),(34.50±0.78)and(36.61±0.34)℃;the thymus indexes were(1.19±0.20),(1.24±0.25),(0.47±0.15)and(1.31±0.21)mg·g-1;the spleen indexes were(1.95±0.33),(2.18±0.28),(1.61±0.27)and(2.29±0.24)mg·g-1.Compared with the model group,the above indexes of the experimental group and the control group were significantly increased(all P＜0.01).A total of 14 potential biomarkers of Honey-processed Hedysari Radix in treating spleen-Qi deficiency syndrome were screened out in this study,which mainly involved amino acid metabolism such as tryptophan and glutamate,riboflavin metabolism and adenosine 5'-monophosphate-activated protein kinase metabolism.Conclusion Honey-processed Hedysari Radix can further protect the intestinal mucosal barrier and reduce the intestinal inflammatory response by improving the metabolic level of cecum contents in rats with spleen-Qi deficiency in cecum contents,thus exerting the effect of strengthening the spleen and tonifying the Qi.

Objective: To analyze the epidemiological characteristics of typhus in China from 1950 to 2021, and discuss the challenges in typhus prevention and control in China and suggest future prevention and control strategies. Methods: Based on the reported data of typhus from 1950 to 2021 in China from the Infectious Disease History Database of China Public Health Science Data Center and the National Notifiable Infectious Disease Reporting Information System of Chinese Center for Disease Control and Prevention, we conducted a descriptive statistical analysis. Mann-Kendall test and circular distribution method were used to analyze the incidence, mortality and case fatality of typhus to reveal the temporal, spatial and population distributions and diagnosis of typhus in China. Results: From 1950 to 2021, a total of 452 965 typhus cases and 7 339 typhus deaths were reported in China, with the cases numbers exceeding 10 000 in 14 years of the 1950s, 1960s and 1980s, respectively. Since 1990s, the reported cases and incidence rate of typhus have decreased dramatically and the most cases were sporadic. However, the reported typhus cases in Anhui, Hubei, Hunan Provinces showed significant uptrends. Although typhus could occur all the year round, but the seasonality was observed with the incidence mainly in summer and autumn. For different provinces from the north to the south, the peaks of typhus' monthly incidence tended to shift to earlier dates. The male to female ratio of the cases was 1.01∶1 (18 529∶18 366). However, more cases occurred in women in recent years. The cases aged ≤9 years accounted for the highest proportion (18.9%), but the number of cases aged ≥50 years showed an upward trend. Most cases were farmers with the proportion increasing year by year. Moreover, the cases in students and scattered-living children also accounted for relatively higher proportions. The median of the interval between onset and diagnosis of typhus was 6 days. Most cases were clinically diagnosed, while the proportion of laboratory-confirmed cases was low and most laboratory cases were confirmed by Well-Felix reaction. Conclusions: Although the incidence and mortality of typhus in China has decreased significantly, the risk for local typhus outbreaks still exists. The prevention and control of typhus still face many challenges. It is indispensable to strengthen the pathogen detection and surveillance for typhus in China.
Child ; Humans ; Male ; Female ; Scrub Typhus/epidemiology* ; Typhus, Epidemic Louse-Borne/epidemiology* ; China/epidemiology* ; Incidence ; Disease Notification

Congenital bilateral absence of the vas deferens (CBAVD) is observed in 1%-2% of males presenting with infertility and is clearly associated with cystic fibrosis transmembrane conductance regulator (CFTR) mutations. CFTR is one of the most well-known genes related to male fertility. The frequency of CFTR mutations or impaired CFTR expression is increased in men with nonobstructive azoospermia (NOA). CFTR mutations are highly polymorphic and have established ethnic specificity. Compared with F508Del in Caucasians, the p.G970D mutation is reported to be the most frequent CFTR mutation in Chinese patients with cystic fibrosis. However, whether p.G970D participates in male infertility remains unknown. Herein, a loss-of-function CFTR p.G970D missense mutation was identified in a patient with CBAVD and NOA. Subsequent retrospective analysis of 122 Chinese patients with CBAVD showed that the mutation is a common pathogenic mutation (4.1%, 5/122), excluding polymorphic sites. Furthermore, we generated model cell lines derived from mouse testes harboring the homozygous Cftr p.G965D mutation equivalent to the CFTR variant in patients. The Cftr p.G965D mutation may be lethal in spermatogonial stem cells and spermatogonia and affect the proliferation of spermatocytes and Sertoli cells. In spermatocyte GC-2(spd)ts (GC2) Cftr p.G965D cells, RNA splicing variants were detected and CFTR expression decreased, which may contribute to the phenotypes associated with impaired spermatogenesis. Thus, this study indicated that the CFTR p.G970D missense mutation might be a pathogenic mutation for CBAVD in Chinese males and associated with impaired spermatogenesis by affecting the proliferation of germ cells.
Humans ; Animals ; Mice ; Male ; Mutation, Missense ; Retrospective Studies ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics* ; Infertility, Male/genetics* ; Mutation ; Vas Deferens/abnormalities* ; Spermatogenesis/genetics*

Background::Transplant renal artery stenosis (TRAS) is a vascular complication after kidney transplantation associated with poor outcomes. This study aimed to analyze the efficacy and safety of low-dose aspirin for preventing TRAS.Methods::After kidney transplantation, patients were enrolled from January 2018 to December 2020 in Henan Provincial People’s Hospital. A total of 351 enrolled recipients were randomized to an aspirin group with low-dose intake of aspirin in addition to standard treatment ( n = 178), or a control group with only standard treatment ( n = 173). The patients was initially diagnosed as TRAS (id-TRAS) by Doppler ultrasound, and confirmed cases were diagnosed by DSA (c-TRAS). Results::In the aspirin and control groups, 15.7% (28/178) and 22.0% (38/173) of the recipients developed id-TRAS, respectively, with no statistical difference. However, for c-TRAS, the difference of incidence and cumulative incidence was statistically significant. The incidence of c-TRAS was lower in the aspirin group compared with the control group (2.8% [5/178] vs. 11.6% [20/173], P = 0.001). Kaplan–Meier estimates and Cox regression model identified the cumulative incidence and hazard ratio (HR) of TRAS over time in two groups, showing that recipients treated with aspirin had a significantly lower risk of c-TRAS than those who were not treated (log-rank P = 0.001, HR = 0.23, 95% confidence interval [CI]: 0.09–0.62). The levels of platelet aggregation rate ( P < 0.001), cholesterol ( P = 0.028), and low-density lipoprotein cholesterol ( P = 0.003) in the aspirin group were decreased compared with the control group in the third-month post-transplantation. For the incidence of adverse events, there was no statistical difference. Conclusion::Clinical application of low-dose aspirin after renal transplant could prevent the development of TRAS with no significant increase in adverse effects.Trial Registration::Clinicaltrials.gov, NCT04260828.

OBJECTIVE: To utilized the baseline data of the Beijing Fangshan Family Cohort Study, and to estimate whether the association between a healthy lifestyle and arterial stiffness might be modified by genetic effects. METHODS: Probands and their relatives from 9 rural areas in Fangshan district, Beijing were included in this study. We developed a healthy lifestyle score based on five lifestyle behaviors: smoking, alcohol consumption, body mass index (BMI), dietary pattern, and physical activity. The measurements of arterial stiffness were brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). A variance component model was used to determine the heritability of arterial stiffness. Genotype-environment interaction effects were performed by the maximum likelihood methods. Subsequently, 45 candidate single nucleotide polymorphisms (SNPs) located in the glycolipid metabolism pathway were selected, and generalized estimated equations were used to assess the gene-environment interaction effects between particular genetic loci and healthy lifestyles. RESULTS: A total of 6 302 study subjects across 3 225 pedigrees were enrolled in this study, with a mean age of 56.9 years and 45.1% male. Heritability of baPWV and ABI was 0.360 (95%CI: 0.302-0.418) and 0.243 (95%CI: 0.175-0.311), respectively. Significant genotype-healthy diet interaction on baPWV and genotype-BMI interaction on ABI were observed. Following the findings of genotype-environment interaction analysis, we further identified two SNPs located in ADAMTS9-AS2 and CDH13 might modify the association between healthy dietary pattern and arterial stiffness, indicating that adherence to a healthy dietary pattern might attenuate the genetic risk on arterial stiffness. Three SNPs in CDKAL1, ATP8B2 and SLC30A8 were shown to interact with BMI, implying that maintaining BMI within a healthy range might decrease the genetic risk of arterial stiffness. CONCLUSION The current study discovered that genotype-healthy dietary pattern and genotype-BMI interactions might affect the risk of arterial stiffness. Furthermore, we identified five genetic loci that might modify the relationship between healthy dietary pattern and BMI with arterial stiffness. Our findings suggested that a healthy lifestyle may reduce the genetic risk of arterial stiffness. This study has laid the groundwork for future research exploring mechanisms of arterial stiffness.
Humans ; Male ; Middle Aged ; Female ; Ankle Brachial Index ; Cohort Studies ; Gene-Environment Interaction ; Vascular Stiffness/genetics* ; Pedigree ; Pulse Wave Analysis/methods* ; Genotype

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective To evaluate the activity of the cerebral glymphatic system during recovery in ischemic stroke(IS)patients with motor dysfunction,and to explore its association with motor function scores and corticospinal tract(CST)integrity via.Methods A total of 20 patients with IS(stroke group)and 20 healthy volunteer(control group)were recruited.There was a single lesion located at the left cerebral hemisphere in the stroke group.Demographic and clinical data of all participants were recorded.All participants underwent brain MRI scans,including diffusion tensor imaging(DTI)and T2WI.Diffusion tensor image analysis along the perivascular space(DTI-ALPS)index at lateral ventricle level,fractional anisotropy(FA)and axial diffusivity(AD)of CST were calculated and the differences of each index between the two groups were compared.The correlation between DTI-ALPS index and Fugl-Meyer score and integrity of CST were analyzed in stroke group,respectively.Results The DTI-ALPS index in the stroke group was significantly lower than that in the control group(t=-3.88,P＜0.001).The DTI-ALPS index in the stroke group was positively correlated with motor function score(P=0.019),motor function grading(P=0.024)and sensory score(P=0.048),respectively.The DTI-ALPS index was negatively correlated with FA(r=-0.60,P=0.009)and AD(r=-0.67,P=0.002)of healthy side CST.Conclusion The decrease of DTI-ALPS index in patients with IS indicates the damage of cerebral glymphatic system.DTI-ALPS index may be a potential MRI biomarker for motor dysfunction in patients with IS,and a new idea is proposed for the study of the pathophysiological mechanism of IS.